Odnos koncentracije i doze takrolimusa kao strategija terapijskog monitoringa leka: uticaj pola i komedikacije
Sažetak
Uvod/Cilj. Kombinacija takrolimusa i drugih lekova kao što su kortikosteroidi, čest je imunosupresivni režim. S druge strane, raste broj dokaza da se muškarci i žene mogu razlikovati u odgovoru na lečenje istim lekom. Cilj ovog rada bio je da se proceni uticaj razlike među polovima i komedikacije na izloženost takrolimusu, uz pomoć odnosa koncentracije i doze (C/D odnos) takrolimusa kod bolesnika sa transplantiranim bubregom. Metode. Ispitivanje je sprovedeno kroz prospektivnu seriju od 54 bolesnika, gde je jedinica posmatranja bio kontrolni ambulantni pregled (1 872) bolesnika sa transplantiranim bubregom. Bolesnici su praćeni od 2010. do 2014. godine, a praćenje je započeto mesec dana nakon transplantacije. Minimalna koncentracija takrolimusa u krvi (tacrolimus trough concentration – TTC) merena je uz pomoć hemiluminiscentnog mikročestičnog imunoeseja. Rezultati. Odnos TTC i C/D bio je značajno niži kod žena nego kod muškaraca. Za razliku od muškaraca, kod žena je nađeno značajno povećanje dnevne doze takrolimusa (TDD) po kg telesne težine i TTC, zajedno sa povećanjem doze kortikosteroida, koje nije bilo praćeno značajnim promenama odnosa C/D. Bolesnici koji su upotrebljavali inhibitore protonske pumpe (većinom pantoprazol), imali su značajno viši TDD po kg telesne težine i TTC, dok je odnos C/D bio značajno niži nego kod bolesnika bez ovog tretmana. Kod bolesnika koji su upotrebljavali blokatore kalcijumovih kanala (pogotovo amlodipina) TDD po kg telesne težine bio je značajno niži, dok je odnos C/D bio značajno viši nego kod bolesnika bez ovog tretmana. Zaključak. Rezultati pokazuju da su žene manje izložene takrolimusu nego muškarci. Kada su posmatrane polne razlike u odnosu na različite doze kortikosteroida, utvrđeno je brže eliminisanje takrolimusa kod žena, osim kada je doza kortikosteroida bila > 0,25 mg/kg. Izloženost takrolimusu u prisustvu pantoprazola bila je značajno manje izražena, dok je u prisustvu amlodipina bila značajno viša nego kod bolesnika koji nisu bili lečeni ovim lekovima.
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